Spatial distribution of beta-klotho mRNA in the mouse hypothalamus, hippocampal region, subiculum, and amygdala

Spatial distribution of beta-klotho mRNA in the mouse hypothalamus, hippocampal region, subiculum, and amygdala
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DOI:
10.1002/cne.25306
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发表时间:
2022-03-02
影响因子:
2.5
通讯作者:
Chee, Melissa J.
Chee, Melissa J.
中科院分区:
医学3区
文献类型:
--
作者:
Bono, Bianca S.;Ly, Nikita K. Koziel;Chee, Melissa J.

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Beta-klotho(KLB)是大脑中内分泌成纤维细胞生长因子(FGF)15/19和FGF 21信号传导所需的辅助受体。Klb在下丘脑中很突出,这与其代谢功能一致,但Klb的不同作用现在正在出现。中心Klb表达低但离散,并且可支配FGF靶向位点。然而,鉴于其低表达,尚不清楚Klb mRNA是否更广泛。我们进行原位杂交标记Klb mRNA,以生成空间图,捕获小鼠下丘脑,海马区,下托和杏仁核内Klb的分布和水平。半定量分析表明,Klb标记的细胞可以表达低,中,或高水平的Klb mRNA。下丘脑Klb杂交是异质性的,在同一区域内吻尾方向不同。大多数Klb标记的细胞被发现在外侧下丘脑区,但室周下丘脑区域,包括视交叉上核,包含最大比例的细胞表达中等或高水平的Klb。我们还发现异源Klb杂交杏仁核和下托,其中Klb是特别不同的中央杏仁核和腹侧下托,分别。相比之下,海马区的Klb标记细胞仅表达低水平的Klb,并且通常在阿蒙角或齿状回的锥体层中发现。在这项研究中确定的Klb标记的区域是一致的,在代谢,味觉偏好,和神经保护的Klb报告的作用。然而,其他已鉴定的位点,包括下丘脑和杏仁核内的位点,可能表明FGF 15/19或FGF 21信号传导的新作用。
Beta-klotho (KLB) is a coreceptor required for endocrine fibroblast growth factor (FGF) 15/19 and FGF21 signaling in the brain. Klb is prominent within the hypothalamus, which is consistent with its metabolic functions, but diverse roles for Klb are now emerging. Central Klb expression is low but discrete and may govern FGF-targeted sites. However, given its low expression, it is unclear if Klb mRNA is more widespread. We performed in situ hybridization to label Klb mRNA to generate spatial maps capturing the distribution and levels of Klb within the mouse hypothalamus, hippocampal region, subiculum, and amygdala. Semiquantitative analysis revealed that Klb-labeled cells may express low, medium, or high levels of Klb mRNA. Hypothalamic Klb hybridization was heterogeneous and varied rostrocaudally within the same region. Most Klb-labeled cells were found in the lateral hypothalamic zone, but the periventricular hypothalamic region, including the suprachiasmatic nucleus, contained the greatest proportion of cells expressing medium or high Klb levels. We also found heterogeneous Klb hybridization in the amygdala and subiculum, where Klb was especially distinct within the central amygdalar nucleus and ventral subiculum, respectively. By contrast, Klb-labeled cells in the hippocampal region only expressed low levels of Klb and were typically found in the pyramidal layer of Ammon's horn or dentate gyrus. The Klb-labeled regions identified in this study are consistent with reported roles of Klb in metabolism, taste preference, and neuroprotection. However, additional identified sites, including within the hypothalamus and amygdala, may suggest novel roles for FGF15/19 or FGF21 signaling.